EEF1A1 is Involved the Regulating Neuroinflammatory Processes in Parkinson's Disease

Background: Studies have reported that the RNA-binding protein Eukaryotic Elongation Factor 1A1 (EEF1A1) is low expressed in the hippocampal region of Alzheimer’s disease (AD). In addition, it is related to PARK2 activity in cells, predicting its importance in neurodegenerative diseases. However, the function of EEF1A1 in Parkinson’s disease (PD) is unclear. Our study’s primary objective was to knock down EEF1A1 in U251 cells and preliminarily explore the role of EEF1A1 in PD neuroinflammation. Methods: To inhibit EEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells. Then, RNA-seq sequencing was used to determine the Differentially Expressed Genes (DEGs) resulting from the EEF1A1 knockdown. Additionally, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to find the biological processes and signaling pathways engaged in the DEGs, as well as to screen for genes associated with neuroinflammatory processes that influence the development of PD. Further Real Time - quantitative Polymerase Chain Reaction (RT-qPCR) validation experiments were performed to confirm the reliability of the sequencing results. Finally, combined with the support of related literature, the molecular mechanism of EEF1A1 in regulating the neuroinflammatory process of PD was initially explored. Results: Analysis using the RNA-seq technique showed that EEF1A1 knockdown could significantly upregulate the expression of IL-6, GDF15, STC1, MT1E, GPNMB, CCL5, MT1X, A2M, and VIP genes at the transcriptional level. These nine highly elevated genes were enriched to signaling pathways linked to inflammatory processes, according to an analysis of GO and KEGG enrichment. Conclusions: EEF1A1 is involved in the regulating of IL-6, GDF15, STC1, MT1E, GPNMB, CCL5, MT1X, A2M, and VIP genes associated with the neuroinflammatory process of PD. Among them, we found that GDF15, STC1, MT1E, MT1X, GPNMB, VIP, and A2M genes were involved in delaying the neuroinflammatory process of PD, while IL-6 and CCL5 were involved in exacerbating the neuroinflammatory process, implicating that EEF1A1 may participate in the regulation of the PD neuroinflammation.

Keywords

EEF1A1

Parkinson's disease

neuroinflammation

RNA-seq

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Fig. 1.

EEF1A1 regulated differential gene expression in U251 cells. (A) After knocking down EEF1A1 in U251 cells, EEF1A1 expression was detected by qRT-PCR. Error bars represent mean $\pm{}$ SEM. ***p $<$ 0.001. (B) EEF1A1 expression quantified by RNA-seq data. Error bars represent mean $\pm{}$ SEM. ***p $<$ 0.001. (C) Sample correlation analysis and PCA results demonstrate the overall transcriptome level differences between EEF1A1 knockdown cells and control cells. (D) Genes were significantly expressed after EEF1A1 knockdown, as shown by the volcano map. (E) Hierarchical clustering of DEGs in the experimental and control groups. Columns on the coordinate axes indicate samples, and rows indicate genes. Different colors represent genes with varying changes og fold. Red means up-regulated expression, while blue means down-regulated expression. EEF1A1, Eukaryotic Elongation Factor 1A1; PCA, Principal Component Analysis; qRT-PCR, quantitative real-time polymerase chain reaction; DEGs, Differentially Expressed Genes; FPKM, fragments per kilobase of exon per million fragments mapped.

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J. Integr. Neurosci. Print ISSN 0219-6352 Electronic ISSN 1757-448X